Thermodynamic dissociation constants of silychristin, silybin, silydianin and mycophenolate by the regression analysis of spectrophotometric data

Mixed dissociation constants of four drug acids, i.e. silychristin, silybinin, silydianin and mycophenolate at various ionic strengths I of range 0.01 and 0.30 and at temperatures of 25 and 37 °C were determined using the SQUAD(84) regression analysis program applied to pH-spectrophotometric titration data. The proposed strategy of an efficient experimentation in a protonation constants determination, followed by a computational strategy for the chemical model with a protonation constants determination, is presented on the protonation equilibria of silychristin. The thermodynamic dissociation constant pK_a^T was estimated by non-linear regression of {pK_a, I} data at 25 and 37 °C: for silychristin pK_a,1^T=6.52(16) and 6.62(1), pK_a,2^T=7.22(13) and 7.41(5), pK_a,3^T=8.96(9) and 8.94(9), pK_a,4^T=10.17(7) and 10.03(8), pK_a,5^T=11.89(4) and 11.63(7); for silybin pK_a,1^T=7.00(4) and 6.86(5), pK_a,2^T=8.77(11) and 8.77(3), pK_a,3^T=9.57(8) and 9.62(1), pK_a,4^T=11.66(3) and 11.38(1); for silydianin pK_a,1^T=6.64(7) and 7.10(6), pK_a,2^T=7.78(5) and 8.93(1), pK_a,3^T=9.66(9) and 10.06(11), pK_a,4^T=10.71(7) and 10.77(7), pK_a,5^T=12.26(5) and 12.14(5); for mycophenolate pK_a^T=8.32(1) and 8.14(1). Goodness-of-fit tests for various regression diagnostics enabled the reliability of parameter estimates to be found.     

Polarographic studies of uranyl complexes with trans-and cis-butenedioic acids

The complexation of uranyl ion with fumaric and maleic acids was investigated by polarography and conductometry. The uranyl complexes of the two isomers differ: with fumaric acid, UO₂(HFum)₂ and UO₂Fum₂^2- were observed whereas with maleic acid, only one chelate, UO₂Mal₂^2-, was obtained. The dissociation constants obtained from the half-wave potential vs. pH plots were pK₁=3.05 and pK₂=4.55 for fumaric acid and pK₁=1.90 and pK₂=5.60 for maleic acid.     

The thermodynamic dissociation constants of methotrexate by the nonlinear regression and factor analysis of multiwavelength spectrophotometric pH-titration data

The mixed dissociation constants of methotrexate — chemically (2S)-2-[(4-{[(2,4-diamino-7,8-dihydropteridin-6-yl)methyl] (methyl)amino}phenyl)formamido]pentanedioic acid (the cas number 59-05-2) at various ionic strengths I of range 0.01–0.4, and at temperatures of 25°C and 37°C, were determined with the use of two different multiwavelength and multivariate treatments of spectral data, SPECFIT32 and SQUAD(84) nonlinear regression analyses and INDICES factor analysis according to a general rule of first, determining the number of components, and then calculating the spectral responses and concentrations of the components. Concurrently, the experimental determination of the thermodynamic dissociation constants was in agreement with its computational prediction of the PALLAS programme based on knowledge of the chemical structures of the drug. The factor analysis in the INDICES programme predicts the correct number of light-absorbing components when the data quality is high and the instrumental error is known. Three thermodynamic dissociation constants were estimated by nonlinear regression of {pK _a , I} data: for methotrexate pK_a1^T= 2.895(13), pK_a2^T= 4.410(14), pK_a3^T= 5.726(15) at 25°C and pK_a1^T= 3.089(15), pK_a2^T= 4.392(12), pK_a3^T= 5.585(11) at 37°C, where the figure in brackets is the standard deviation in last significant digits. The reliability of the dissociation constants of the drug were proven by conducting goodness-of-fit tests of the multiwavelength spectrophotometric pH-titration data.      

Acid-Base and Photochemical Reactions of Selenious Acid

Abstract

Spectrophotometric data used in connection with H_A acidity function yield pK₁=?3.3(K₁= [H₂SeO₃][H⁺]/[H₃SeO₃ ⁺]);potentiometric and spectral measurements give for pK₂ and pK₃ data in agreement with the literature. At pH > 10 selenite undergoes a fast photochemical reaction, preceded by a rapidly established acid-base equilibrium. Products of this reaction undergo a slow reaction which is second order in selenite.     

The catalytic effect of catiohic amino micelles on the hydrolysis of substituted phenyl esters

The catalytic effects of two aminocationic micelles on the hydrolysis of substituted phenyldecanoate esters and a positively charched benzoate ester (CPNBA) were determined. The micellaric catalysts were of the general structure [CH₃(CH₂)₃N(CH₃)₂(CH₂)_nNH₂]Br where n=2 (micelle 1); n=3 (micelle 2). The kinetics followed the expression: k_obs =k_o+k_cat x K_a/(K_a+H⁺)+k^o_OH[OH^-]. From the comparison of the kc OH rates with specific base catalysis rates deduced from reactions in non catalytic micelles, it was concluded that the kc OH term, is compatible mainly with an aminolysis reaction catalyzed by hydorxide ion. The Hammett and Bronsted correlations (p=2.8; β=1.0), in addition to the very small deuterium isotope effect, suggested that kcat corresponded with a nucleophilic mechanism. The Bronsted plot of log k_cat vs pKa of the phenolate leaving groups in micelles 1 and 2 showed a biphasic behaviour. The break in the curve occured at pK_o=5.89 and pK_o=6.78 respectively. The partition ratio k^±/k_-a of the zwiterionic tetrahedral intermediate was derived from the experimental data and produced the following correlation: log k^±/k_-a=-0.92pK_o+0.43pK_N+2.466. The ester CPNBA exhibited a deuterium isotope effect of 2.1. From product analysis it was concluded that the reaction proceeds via a general base catalysis of aminolysis.     

Spectrophotometric investigation of protolytic equilibria of rutin

The dissociation constants of rutin in aqueous-methanol medium (6040 v/v), the values of which are pK₁=–2.92±0.06, pK₂=6.72±0.11, pK₃=8.26±0.05, pK₄=12.57±0.09, were estimated by using the spectrophotometric method. They were ascribed to the dissociation of protonated oxygen atom at position 1 and then to hydroxyl groups at positions 7, 4', 5, respectively. Resonance structures of H₃L^– ion of rutin were suggested and, by using them, the greater dissociability of the hydroxyl group at position 7 in relation to the –OH group at position 4' was explained.     

Kinetics and mechanism of the base hydrolysis of thecis-chlorobis(ethylenediamme)(benzimidazole)cobalt(III) cation

Summary The hydrolysis ofcis-[CoCl(en)₂(bzmH)]²⁺ (en=ethylenediamine, bzmH=benzimidazole) has been studied over the pH range 8.31–11.58 at I=0.1 mol dm^–3 and 25°. Potentiometric titration of aqueous solutions of the [Co(en)₂(bzmH)OH₂]³⁺ complex obtained by silver(I) catalysed aquation of the chloro-complex give pK₁=5.81 and pK₂ = 8.84 for Equilibria (1) and (2) at 25° and I=0.1 mol dm^–3. Spectrophotometric titration of the hydroxy complex also gives a value of pK₂=8.88 for the ionisation of the coordinated benzimidazole. The kinetic data can be interpreted in terms of base hydrolysis ofcis-[CoCl(en)₂(bzmH)]²⁺ (k_OH=220 dm³ mol^–1s^–1) andcis-[CoCl(en)₂(bzm)]⁺ (k_OH=14.9 dm³ mol^–1s^–1). Comparisons with the corresponding imidazole and pyridine complexes are made.     

Reaktivität der Pyrrolpigmente, 2. Mitt.: Deprotonierung von 3-Pyrrolin-2-onen

Deprotonation of 3,4-dimethyl-3-pyrrolin-2-on (1) int-butyl alcohol/potassiumt-butoxide solutions takes place on the N atom, as shown by¹H/²H exchange andpK _a determinations of1 (pK=17.1), 1,3,4-trimethyl-3-pyrrolin-2-one (pK _a =17.6), and 3,4-dimethyl-5-methoxy-2_H-pyrrole (pK _a =16.7). The SCF-MO approximation MINDO/3 indicates, however, that in the gas phase deprotonation of1 should occur at the C atom.

1.Mitt.:Ribó, J. M., Trull, F., Mh. Chem.110, 201 (1979).     

Study of the retention mechanism of uranium on titanium oxide

We have studied the phenomenon of retention of uranium, as a carbonato complex UO₂(CO₃) ₃ ⁴⁻ on titanium oxide. We first proposed a method for preparing titanium oxide whose ion-exchange capacities (2.9 meq Na⁺/g, 0.11 meq UO ₂ ²⁺ /g) and physical properties (mechanical resistance and granulometry) make it quite suitable for liquid chromatography and particularly for the extraction process of uranium from sea-water. We prepared the sodium tricarbonatouranate, the major form of uranium in sea-water. We studied the retention of this compound on titanium oxide. From a thermodynamic study of the retention equilibrium we proposed a retention mechanism of the ligang-exchange type: uranyl is retained on titanium oxide, surrounded with two CO ₃ ²⁻ ligands and two ≥TiO⁻ ligands. We shown that 2/3 of the exchanged hydroxyl groups have pK_H1=4.9 and 1/3 of them have pK_H2=9.3.     

Multifunctional substances — Determination of pKa-values in overlapping ranges using an iteration procedure

Summary In multifunctional substances, pK_a-values from different functional groups may overlap. Therefore, systematically wrong results are obtained, if pK_a-values are used from titration charts without appropriate corrections. The iteration procedure presented in this article starts with the pK_a-values at the half-way neutralisation points. From these preliminary values, new positions in the charts are calculated, from which better approximations of the pK_a-values are obtained. These steps are repeated several times, until the results converge. Cefodizime (HR 221) with three acid/base functional groups was used as model substance. The disodium salt was titrated using three molar equivalents of 0.1 mol/l hydrochloric acid. Using the iteration procedure, three pK_a-values were obtained from the titration chart: 1. The amino-function: pK₁=2.85; 2. the first carboxyl-function: pK₂=3.37; 3. the second carboxyl-function: pK₃=4.18.     

The Protonation and Deprotonation Equilibria of Hypericin Revisited

 The protonation and deprotonation behaviour and the assignment of pK _a values of hypericin are reviewed and discussed. Three experiments (electrospray MS, ¹H NMR, acid–base indicator equilibria) provided additional evidences for the assignment of pK _a values of −5 and −6 to mono- and diprotonation at the carbonyl groups of hypericin, of pK _a = 2 to monodeprotonation at the bay-region, and of pK _a = 11 to dideprotonation at the bay- and peri-regions.     

Effects of Aerosol-OT reversed micelles in carbon tetrachloride on acid-base indicator equilibria

ApparentpK _a values of thymol blue solubilized in Aerosol-OT reversed micelles in carbon tetrachloride at 25 °C were determined spectrophotometrically. The effects of the Aerosol-OT concentration and the (water)/(surfactant)R ratio were investigated. The apparentpK _a values increase as a function of increasing (R). All the measuredpK _a values are less than that in water. The decrease ranges from 1.23 units (detergent=0.4 M,R=1.39) to 0.42 units (Aerosol-OT=0.6 M,R=9,25). These results are rationalized in terms of decreased hydronium ion activity in the micellar core due to its binding to the detergent SO₃ ^? groups.     

Study of the Electrochemical Behavior of Disperse Blue 1‐Modified Graphite Electrodes. Application to the Flow Determination of NADH

The preparation and the electrochemical study of Disperse Blue 1‐chemically modified electrodes (DB1‐CME), as well as their efficiency for the electrocatalytic oxidation of NADH is described. The proposed mediator was immobilized by physical adsorption onto graphite electrodes. The electrochemical behavior of DB1‐CME was studied with cyclic voltammetry. The electrochemical redox reaction of DB1 was found to be reversible, revealing two well‐shaped pair of peaks with formal potentials 152 and ?42 mV, respectively, (vs. Ag/AgCl/3M KCl) at pH 6.5. The current I_p has a linear relationship with the scan rate up to 800 mV s^?1, which is indicative for a fast electron transfer kinetics. The dissociation constants of the immobilized DB1 redox couple were calculated pK₁=4 and pK₂=5. The electrochemical rate constants of the immobilized DB1 were calculated k₁°=18 s^?1 and k₂°=23 s^?1 (Γ=2.36 nmol cm^?2). The modified electrodes were mounted in a flow injection manifold, poised at +150 mV (vs. Ag/AgCl/3M KCl) and a catalytic current due to the oxidation of NADH was measured. The reproducibility was 1.4% RSD (n=11 for 30 μM NADH) The behavior of the sensor towards different reducing compounds was investigated. The sensor exhibited good operational and storage stability.     

The Protonation and Deprotonation Equilibria of Hypericin Revisited

Summary.  The protonation and deprotonation behaviour and the assignment of pK _a values of hypericin are reviewed and discussed. Three experiments (electrospray MS, ¹H NMR, acid–base indicator equilibria) provided additional evidences for the assignment of pK _a values of −5 and −6 to mono- and diprotonation at the carbonyl groups of hypericin, of pK _a = 2 to monodeprotonation at the bay-region, and of pK _a = 11 to dideprotonation at the bay- and peri-regions. Received September 26, 2001. Accepted October 1, 2001     

Equilibria in solutions of methanol or ethanol,sulfuric acid,and alkyl sulfates

Equilibria in reactions of methanol and ethanol with sulfuric acid or in hydrolyses of alkyl sulfates were followed using ¹³C NMR, anion-exchange HPLC, and titrations. Variations of equilibrium constant K = [ester][H₂O]/[ROH][HSO₄^-] with acidity indicate participation of reactions ROH₂⁺ + HSO₄^- ⇌ ROH⁺SO₃^- + H₂O, accompanied by acid base equilibria involving the alcohol and the ester. For mixtures containing initially 20% (w/w) alcohol, pK_MeOH2 + = −4.2, pK_EtOH2+ = −3.7, pK_MeOH+_SO3- = −3.3 and pK_EtOH+_SO3- = −2.7.     

On oxoacidic properties and solubilities of beryllium and magnesium oxides in molten (CsCs + KCl + NaCl) eutectic at T = 783 K

Reactions of Be²⁺ and Mg²⁺ with O^2– in molten eutectic mixture (CsCs + KCl + NaCl) (0.455:0.245:0.30) at T = 783 K were studied by a potentiometric method using Pt(O₂)|ZrO₂(Y₂O₃) indicator electrode. Addition of O^2– ions to the melt containing Mg²⁺ results in precipitation of MgO (pK_s,MgO = 11.89 ± 0.3, molality) whereas interaction of Be²⁺ with O^2– is accompanied with sequential formation of Be₂O²⁺ (pK = 15.68 ± 0.5, molality) and precipitation of BeO (pK_s,BeO = 9.62 ± 0.3, molality). On the basis of the obtained and known data pK_s,MgO–T⁻¹ dependence in molten (CsCs + KCl + NaCl) eutectic is constructed. The slope of the said dependence in T/K = (from 583 to 1073) range is in good agreement with the value predicted by the Shreder equation, that extends the range of use of the Shreder equation for predictions of metal oxide solubilities in molten halides.     

Acid properties of some phosphonocarboxylic acids

Thermodynamic acid dissociation constants were determined for phosphonoacetic acid (PAA) in aqueous solution at 25°C by coulometric titrations at different ionic strengths and extrapolation of the results to I=0. The respective values are pK₁2.0, pK₂=5.11±0.04, and pK₃=8.69±0.05. The enthalpy and entropy of dissociation for the second and the third dissociation steps, determined from the temperature dependence of pK's, are H ₂ ^o =0.2±0.3 kcal-mole^–1, S ₂ ^o =22.6±0.9 e.u., H ₃ ^o =1.3±0.4 kcal-mole^–1, and S ₃ ^o =11.7±0.4 e.u. Phosphorus-31 and carbon-13 NMR studies of PAA solutions as a function of pH gave the deprotonation sequence of the triacid. Acidity constants were also determined for phosphonoformic acid, 2-phosphonopropionic acid, and 3-phosphonopropionic acid at an ionic strenght of 0.05.To whom correspondence should be addressed.     

Polarography of Uranium Chelate with 2,3-Cresotic Acid

The polarography of uranyl ion in 2,3-cresotic acid solution has been studied at 25°C under varying conditions of ligand concentration and pH. The ligands species were proved to be a 2,3-cresotate anion. The half-wave potential vs. pH value interpreted on the basis of pK value for the acid ionization, and resulted in agreement with the deduction. The mole ratio of metal to ligand was found to be 1:1 and 1:2 by conductometric titration. At pH < pK₁, the complex species of UO₂(H₂A)²⁺ and UO₂(HA)⁺ was identified. At pK₁ < pH < pK₂, the co-existence of UO₂(HA)⁺, UO₂(OH)(HA)₂^? and UO₂(A)₂^2– was confirmed. At pH > pK₂, the complex species of UO₂(OH) (A)₂^3– was formed.     

Unexplored metallic cation effect in the acidity constants of p-t-butylthiacalix[4]arene,p-t-butylcalix[4]arene and p-t-butylcalix[6]arene in aqueous-organic media

The influence of the metallic cation of the base (Li⁺, Na⁺ or K⁺) was determined on the acid–base constants of p-t-butylthiacalix[4]arene (TC4), p-t-butylcalix[4]arene (CA4) and p-t-butylcalix[6]arene (CA6) in ethanol/water in an large interval of pH values by potentiometry and spectrophotometry. The pK_a values determined by both methods correlate very well and these are characteristic for each macrocycle with influence of the cation of the base without a straight evidence of an effect by the size of the metallic cation. In the case of TC4, pK_a1 and pK_a2 were lower to Li⁺ and Na⁺ than with K⁺. For CA4, an effect of K⁺ on the pK_a2 with respect to Li⁺ was observed. A very different behaviour was observed for CA6 with Li⁺ and K⁺ showing a lower pK_a2 and a higher pK_a3 than with Na⁺. These effects were interpreted on the basis of the interaction/complexation of each cation with each macrocycle.